Mitral regurgitation is the most common heart valve problem encountered in clinical practice. Mitral valve repair is considered superior to mitral valve replacement, and there many surgical techniques utilized to address differing pathologies. One approach to assess the effects of pathology and proposed surgical repair is to utilize a computational model, in which pathologic or surgical alterations can be assessed systematically. However, current models are limited by assumptions related to geometry and material properties and importantly, none have been validated with detailed experimental data. In this proposal, we will utilize an advanced fluid-structure interaction (FSI) model of the mitral valve system that allows analysis of the valve in the normal, diseased, or repaired states. The findings will be validated utilizing a well-established, but unique experimental in-vitro system, in which mitral valve function can be extensively assessed. Once validated, this FSI model can be utilized to assess many different types of pathology and repair. We have chosen to assess two pathologic conditions (annular dilatation, papillary displacement) and one type of repair (percutaneous edge-to-edge repair) in both the diastolic or systolic phases. The specific aims of this proposal are: 1. Normal model validation: Geometry of an established FSI model will be adapted to match the geometry obtained from the 5 normal valves to be utilized in the in-vitro system. The model will be refined and optimized via an inverse analysis. The effect of varying geometry on valvular displacement, stress, strain, fluid velocity and streamlines in the FSI model will be assessed, and compared directly to the data obtained from the in-vitro system. 2. Pathologic condition assessment: FSI models will be created for relevant pathologic conditions which are proposed to be suitable for percutaneous edge-to-edge repair. These are: a) Annular dilatation alone, b) Annular dilatation with symmetric PM displacement, c) Annular dilatation with asymmetric PM displacement. 3. Repair assessment: The FSI models for annular dilatation with PM displacement will be utilized to assess the effect of edge-to-edge repair on valve function, mechanics and fluid flow. Variations of the edge-to-edge repair to be assessed are: a) Central ETE clip (imposed on MV with annular dilatation with symmetric PM displacement), b) Off-centered ETE clip (imposed on MV with annular dilatation with asymmetric PM displacement) The ultimate long term goal of this research (beyond the scope of the current proposal) is to provide an advanced fluid-structure interaction model of the mitral valve that could ultimately be used for individualized patient planning for mitral valve repair. PUBLIC HEALTH RELEVANCE: We will utilize an advanced fluid-structure interaction (FSI) model of the mitral valve system that allows analysis of the valve in the normal, diseased, or repaired states. The findings will be validated utilizing a well- established, but unique experimental in-vitro system, in which mitral valve function can be extensively assessed. We have chosen to assess two pathologic conditions (annular dilatation, papillary displacement) and one type of repair (percutaneous edge-to-edge repair) in both the diastolic or systolic phases. Once validated, this FSI model can be utilized to assess many different types of pathology and repair. The ultimate long term goal of this research (beyond the scope of the current proposal) is to provide an advanced fluid- structure interaction model of the mitral valve that could ultimately be used for individualized patient planning for mitral valve repair.